The objectives of the research proposal are (1) to determine the effect of ethanol ingestion on hepatic collagen metabolism and (2) to study the enzymatic nature of microsomal ethanol oxidation. The effect of ethanol on hepatic collagen metabolism will be investigated in animals and humans. Studied in animals will be the effect of ethanol ingestion on (a) collagen deposition by examination of liver morphology and contents of collagen hydroxyproline; (b) collagen synthesis, as measured by the hepatic activity of protocollagen proline hydroxylase and the incorporation of proline into collagen and (c) collagen degradation by measurement of urinary excretion of peptide bound hydroxyproline and acid mucopolysaccharides, and the activities of hepatic collagenase and lysosomal enzymes. The activity of hepatic protocollagen proline hydroxylase and the urinary excretion of peptide bound hydroxyproline and acid mucopolysaccharides will be assayed in patients with alcoholic hepatitis to determine (a) if these parameters are of predictive value in the development of cirrhosis and (b) the effects of prednisolone and penicillamine therapy. Samples are being received from double-blind controlled studies of the effects of these drugs on alcoholic hepatitis carried out by other investigators. The nature of the ethanol oxidizing activity will be studied by further purification of microsomal fractions of cytochrome P-450, cytochrome c reductase, and lipid, followed by reconstitution experiments to determine if these components are indeed responsible for the ethanol oxidizing activity or if another enzyme system is active in ethanol oxidation by microsomes.